Diecyclene, pills 2mg+0.03mg 21pcs

Composition

of 1 tab. :

– ethinyl estradiol 0.03 mg

-dienogest 2 mg

Pharmacological action

Pharmaceutical group:

contraceptive (estrogen+progestogen).

Pharmaceutical effect:

Diecyclene is a low-dose monophasic oral hormonal contraceptive. The contraceptive effect is based on the interaction of various factors, the most important of which is the inhibition of ovulation and a change in the viscosity of the cervical mucus, as a result of which it becomes impervious to spermatozoa, and the penetration of spermatozoa through the cervical canal is difficult. When used correctly, the Pearl index (a measure that reflects the number of pregnancies in 100 women using a contraceptive during the year) is less than 1. If you skip pills or use them incorrectly, the Pearl index may increase.

In addition to the contraceptive effect, it also has other concomitant positive properties. In women taking combined oral contraceptives, the cycle becomes more regular, the soreness, intensity and duration of menstrual-like bleeding decreases, resulting in a reduced risk of iron deficiency anemia. There is also evidence of a reduced risk of endometrial and ovarian cancer.

The progestogen component of dienogest is an active progestogen, it is a derivative of nortestosterone with antiandrogenic activity and has a positive effect on the lilide profile, increasing the concentration of high-density lipoproteins (HDL).

Pharmacokinetics:  

Ethinyl Estradiol: When taken orally, it is rapidly and completely absorbed. The maximum concentration of estradiol in the blood plasma (about 67 pg/ml) is reached in 1.5-4 hours. After absorption and the “first pass” effect through the liver, ethinyl estradiol is metabolized, its absolute bioavailability with oral use is about 44%.

Ethinyl Estradiol binds significantly to serum albumin (approximately 98%) and induces the synthesis of sex hormone-binding globulin (SHBG) in blood plasma. The volume of distribution of ethinyl estradiol is about 2.8-8.6 l / kg.

Ethinyl estradiol undergoes presystemic conjugation both in the small intestine mucosa and in the liver. The main pathway of metabolism is aromatic hydroxylation with the formation of many hydroxylated and methylated derivatives in the form of free metabolites, glucuronide metabolites and sulfates. The rate of clearance from blood plasma is approximately 2.3-7 ml / min / kg.

Up to 30-50% of the metabolites of ethinyl estradiol a are excreted by the kidneys,30-40% – through the intestines. The half-life of zradiol (T1 / 2) does not exceed 10 hours after a single dose of 1 tablet and increases to 15 hours after 3 cycles of taking the drug. The equilibrium concentration of ethinyl estradiol in the blood plasma with regular use is reached in the second half of the cyclic use of the drug.

Dienogest:

When taken orally, it is rapidly and almost completely absorbed. The maximum concentration of dienogest in the blood serum (about 51 pg/ml) is reached after 2.5 hours. The absolute bioavailability of dienogest is 96%, the equilibrium concentration in the blood plasma with constant intake is reached after 4 days.

90% of the total plasma concentration of dienogest binds to serum albumin, but does not bind to SHBG or corticosteroid-binding globulin. In an unbound form,10% of the total concentration of dienogest in blood plasma is found. The volume of distribution of dienogest is about 37-45 liters.

It is primarily metabolized by hydroxylation, but also by hydrogenation, conjugation, and aromatization to form inactive metabolites. After taking a single dose, the total clearance of dienogest is about 3.6 l / h. After taking a dose of 0.1 mg / kg, the ratio of excretion of dienogest in the form of metabolites by the kidneys and through the intestine is 3: 1. Only a small amount of unchanged dienogest is excreted by the kidneys. The half-life (T1/2) of dienogest is approximately 8.5-10.8 h. After oral use,86% of the dienogest dose is excreted within 6 days; a significant part of it is excreted in the first 24 hours after ingestion mainly by the kidneys.

Equilibrium concentration. Induction of globulin synthesis by ethinyl estradiol does not affect the pharmacokinetics of dienogest With daily use of the drug, the concentration of dienogest in serum increases by 1.5 times.

Indications

-oral contraception; – treatment of mild to moderate acne and seborrhea.

Contraindications

-hypersensitivity to any of the components of the drug Diecyclene;- thrombosis (venous and arterial) and thromboembolism currently or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, cerebrovascular disorders);- conditions that precede thrombosis (including transient ischemic attacks, angina pectoris) at the present time or in the anamnesis;— multiple or pronounced risk factors for venous or arterial thrombosis, including complicated lesions of the valvular heart apparatus, atrial fibrillation, vascular diseases of the brain or coronary arteries; uncontrolled arterial hypertension, volume surgery with prolonged immobilization, smoking over the age of 35 years, obesity with a body mass index > 30 kg / m2— – diabetes mellitus with diabetic angiopathy;- identified predisposition to venous or arterial thrombosis, including resistance to activated protein C, antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia, phospholipid antibodies, lupus antigen;- severe liver diseases (until recovery and normalization of laboratory parameters of liver function);- benign or malignant liver tumors, including in the anamnesis;— severe forms of arterial hypertension with blood pressure >160/100 mm Hg; – revealed hormone-dependent malignant diseases of the genitals or mammary glands or suspected of them, including in the anamnesis;- bleeding from the vagina of unknown origin; – migraine with focal neurological symptoms at the present time or in the anamnesis;- pancreatitis accompanied by severe hypertriglyceridemia at the present time or in the anamnesis;- severe and / or acute renal failure;— pregnancy or suspected pregnancy; – lactation period;- hereditary lactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome or hypersensitivity to peanuts or soy (due to the presence of Diecyclene lactose and soy lecithin in the preparation). With caution: Risk factors for developing thrombosis and thromboembolism: obesity, smoking, dyslipoproteinemia, arterial hypertension, migraine without focal neurological symptoms, heart valve defects, prolonged immobilization, serious surgery, extensive trauma, hereditary predisposition to thrombosis (thrombosis, myocardial infarction or impaired cerebral circulation at a young age in one of the closest relatives). Other diseases that may cause peripheral circulatory disorders include diabetes mellitus without diabetic angiopathy, superficial venous phlebitis, systemic lupus erythematosus (SLE), hemolytic-uremic syndrome, Crohn’s disease, ulcerative colitis, and sickle cell anemia. Diseases that first occurred or worsened during pregnancy or during previous use of sex hormones, for example, jaundice and / or pruritus due to cholestasis, gallbladder diseases, porphyria, Sydenham’s chorea, herpes during pregnancy in the anamnesis, hearing loss (associated with otosclerosis). Endogenous depression, epilepsy; hereditary angioedema; hypertriglyceridemia; liver diseases; postpartum period.

Interaction

Some medications can increase the rate of metabolic clearance of sex hormones and lead to severe bleeding or to a decrease in the contraceptive effect of the drug. Similar effects are typical for drugs that induce microsomal liver enzymes: hydantoin, barbiturates, primidone, carbamazepine and rifampicin. There are also suggestions for rifabutin, efavirenz, nevirapine, oxcarbazenin, topiramate, felbamate, ritonavir, nelvinafir, fizeofulvin, as well as drugs containing St. John’s wort (Hypericum perforatum). Some antibiotics that reduce the intestinal-hepatic circulation of estrogens (such as ampicillin or tetracycline) reduce the effectiveness of combined oral contraceptives.

Women taking short courses (maximum 1 week) of the above medications should resort to additional contraceptive measures (for example, the barrier method) during the period of simultaneous use of the drugs and for the next 7 days.

When using oral contraceptives with rifampicin at the same time, additional contraceptive measures (for example, the barrier method) should be resorted to during the simultaneous use of drugs and in the next 4 weeks after discontinuation of treatment. If the package of oral contraceptives ends before the end of the course of use of other drugs, tablets from the next package of the drug should be taken without interruption.

It is necessary to increase the dose of contraceptives with a long-term course of treatment with drugs that induce microsomal liver enzymes. In case of side effects (for example, irregular menstruation) or ineffectiveness of the drug, you should additionally use other non-hormonal contraceptives. Oral contraceptives may affect the metabolism of some other medications.Accordingly, this may lead to an increase in (cyclosporine) or decrease (lamotrigine) their concentration in plasma or tissues.

Dienogest is a substrate of cytochrome P450 (CYP3A4). Known CYP3A4 inhibitors, such as antifungal medications (e. g., ketoconazole), cimetidine, verapamil, macrolides (e. g., erythromycin), diltiazem, antidepressants, and grapefruit juice, may increase the concentration of dienogest in blood plasma.

How to take, course of use and dosage

Inside, daily, preferably at the same time, in the order indicated on the package, with a small amount of water. Take 1 tablet a day continuously for 21 days. Taking tablets from each subsequent package begins after a 7-day break, during which there is “withdrawal” bleeding (menstrual-like bleeding). It usually begins 2-3 days after taking the last tablet and can continue until the start of taking the new package of tablets. In the absence of taking any hormonal contraceptives in the previous month, taking the drug begins on the first day of the menstrual cycle (on the first day of menstrual bleeding). It is allowed to start taking on the 2nd-5th day of the menstrual cycle, but in this case it is recommended to additionally use a barrier method of contraception during the first 7 days of taking tablets from the first package.

When switching from the previous use of other combined oral contraceptives, it is preferable to start taking the drug the day after taking the last active tablet from the previous package, but not later than the next day after the usual 7-day break in taking (for drugs containing 21 tablets) or after taking the last inactive tablet (for drugs containing 28 tablets in a package).

When switching from a vaginal ring to a transdermal patch, it is preferable to start taking Diecyclene on the day of removal of the ring or patch, but not later than the day when a new ring should be inserted or a new patch should be applied. When switching from contraceptives containing only progestogens (“mini-pili”, injectable forms, implant), the drug is taken: from “mini-pili” – on any day (without a break), from the implant – on the day of its removal, from the injection form-from the day when the next injection should have been made. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills.

After an abortion in the first trimester of pregnancy, you can start taking medication immediately. If this condition is met, there is no need for additional contraceptive protection.

After delivery or abortion in the second trimester of pregnancy, it is recommended to start taking the drug Diecyclene on 21-28 days after delivery or abortion If the reception is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the tablets. However, if the woman has already had sexual activity, pregnancy should be excluded before taking the medication, or it is necessary to wait for the first menstruation. Recommendations in case of irregular use of the drug Diecyclen:

If the delay in taking the pill is less than 12 hours, the contraceptive protection is not reduced. You should take the pill as soon as possible, and the next pill is taken at the usual time. If the delay in taking the pill is more than 12 hours, the contraceptive protection may be reduced.

In the first 2 weeks of taking the drug, if the interval from the time of taking the last tablet is more than 36 hours: take the last missed tablet as soon as possible (even if this means taking 2 tablets at the same time). The next pill is taken at the usual time. Additionally, a barrier method of contraception (condom) should be used for the next 7 days. If there was sexual intercourse within 1 week before skipping the pill, the probability of pregnancy should be taken into account. The more pills you skip and the closer that skip is to the 7-day break from taking the drug, the higher the risk of pregnancy.

At the 3rd week of taking the drug, if the interval from the last tablet is more than 36 hours: take the last missed tablet as soon as possible (even if this means taking 2 tablets at the same time). The next pill is taken at the usual time. Additionally, a barrier method of contraception (condom) should be used for the next 7 days. In addition, taking a tablet from a new package should be started as soon as the current package is finished, i. e. without interruption. Most likely, there will be no “withdrawal” bleeding until the end of taking tablets from the second package, but there may be “smearing” discharge or uterine bleeding “breakthrough” on the days of taking tablets.

If a woman missed taking a pill and then during a break in taking the drug she does not have “withdrawal” bleeding, pregnancy should be excluded.

For gastrointestinal disorders:

If a woman has had vomiting or diarrhea within 3 to 4 hours after taking Diecyclen, the absorption may be incomplete. In this case, you need to follow the recommendations regarding skipping taking the pill. If a woman does not want to change the normal mode of taking the drug, she should take an additional tablet from the spare package if necessary. Changing the day of onset of menstrual-like bleeding:

To delay the onset of menstrual bleeding, it is necessary to continue taking tablets from the new package immediately after taking all the tablets from the previous one, without a break in reception. Tablets from a new package can be taken until the package is finished. Against the background of taking the drug from the second package, a woman may have “smearing” discharge or uterine bleeding “breakthrough”.

Resume taking the drug from the new pack after the usual 7-day break. In order to move the day of the onset of menstrual-like bleeding to another day of the week, it is necessary to reduce the next break in taking Diecyclene tablets by as many days as it is necessary to move the day of the onset of menstrual-like bleeding. The shorter the interval, the higher the risk of no “withdrawal” bleeding and the appearance of further “smearing” discharge and “breakthrough” bleeding while taking tablets from the second package (as well as in the case of delaying the onset of menstrual-like bleeding).

Overdose

Possible symptoms of Diecyclen overdose include nausea, vomiting, irregular spotting, and the absence of menstrual-like bleeding.

If necessary, symptomatic therapy is performed.

Special instructions

Irregular use can lead to acyclic bleeding and reduce the contraceptive effectiveness of the drug. Before starting or resuming the use of the drug, it is recommended to conduct a thorough general medical and gynecological examination (including breast examination and cytological examination of scrapings from the cervix), to exclude pregnancy. In addition, violations of the blood coagulation system should be excluded. When using the drug, it is necessary to conduct preventive control examinations at least once every 6 months.

The drug Diecyclen does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Diseases of the cardiovascular system:

Venous thromboembolism (VTE) may occur in the form of deep vein thrombosis and/or pulmonary embolism when using hormonal contraceptives. The approximate rate of VTE in women taking oral contraceptives with a low dose of estrogens (less than 50 micrograms of ethinyl estradiol) is up to 4 per 10 thousand women per year, compared with 0.5-3 per 10 thousand women who do not use oral contraceptives. However, the frequency of VTE that develops when taking combined oral contraceptives is less than the frequency of VTE associated with pregnancy (6 per 10 thousand pregnant women per year). Extremely rare cases of thrombosis of other blood vessels, such as hepatic, mesenteric, renal arteries and veins, or retinal veins and arteries, have been reported in women taking combined oral contraceptives. The association of these cases with the use of combined oral contraceptives has not been proven. A woman should stop taking the drug and consult a doctor if symptoms of venous or arterial thrombosis develop, which may include unilateral lower limb pain and/or swelling; sudden severe chest pain; with or without radiation to the left arm; sudden shortness of breath; sudden coughing attacks; any unusual, severe, prolonged headache; increased frequency and severity of migraines; sudden partial or complete loss of vision; diplopia; slurred speech or aphasia; dizziness; collapse with or without without a partial seizure; weakness or very significant loss of sensation, suddenly appearing on one side or in one part of the body; movement disorders; “sharp” stomach.

The risk of thrombosis (venous and/or arterial) and thromboembolism is increased: with age, Smoking (with increasing number of cigarettes smoked or the increasing age the risk further increases, especially in women older than 35 years), in the presence of a family history (i. e. venous or arterial thromboembolism ever in close relatives or parents at a relatively young age), obesity, dyslipoproteinemia, hypertension, diseases of the heart valves, prolonged immobilization, extensive surgical intervention, any surgery on the lower limbs or extensive trauma, atrial fibrillation.

In case of prolonged immobilization, in case of serious surgical intervention, any leg surgery or extensive injury, it is advisable to stop using the drug (in the case of planned surgery, at least 4 weeks before it) and not resume taking it for 2 weeks after the end of immobilization.

The possible role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism remains controversial. An increased risk of postpartum thromboembolism should be considered.

Microcirculation disorders can also occur in diabetes mellitus, SLE, hemolytic-uremic syndrome, Crohn’s disease, ulcerative colitis and sickle cell anemia.

Tumors:

The most significant risk factor for cervical cancer is persistent papillomavirus infection. There are reports of a slight increase in the risk of cervical cancer with prolonged use of combined oral contraceptives. However, the association with the use of combined oral contraceptives has not been proven. The possibility of interrelation of these data with screening of cervical diseases and with the peculiarities of sexual behavior (more rare use of barrier methods of contraception) is discussed.

A meta-analysis of 54 epidemiological studies showed that there is a slightly increased relative risk of breast cancer diagnosed in women currently taking combined oral contraceptives (relative risk 1.24). The increased risk gradually disappears within 10 years after discontinuation of these medications. Because breast cancer is rare in women under the age of 40, the increase in breast cancer diagnoses among women who are currently or have recently taken combined oral contraceptives is insignificant relative to the overall risk of this disease. The relationship between the development of breast cancer and the use of combined oral contraceptives has not been proven. The observed increased risk may also be due to careful monitoring and earlier diagnosis of breast cancer in women using combined oral contraceptives. Women who have ever used combined oral contraceptives are more likely to develop early-stage breast cancer than women who have never used them.

In rare cases, against the background of the use of combined oral contraceptives, the development of benign, and in extremely rare cases, malignant liver tumors was observed, which in some cases led to life-threatening intra-abdominal bleeding. If there is severe abdominal pain, enlarged liver, or signs of intra-abdominal bleeding, this should be taken into account when making a differential diagnosis.

Other states:

Women with hypertriglyceridemia or a family history of it may have an increased risk of developing pancreatitis when taking combined oral contraceptives.

Although a small increase in blood pressure (BP) has been reported in many women taking combined oral contraceptives, clinically significant increases have rarely been observed. The relationship between the use of combined oral contraceptives and increased blood pressure has not been established, however, if persistent, clinically significant arterial hypertension develops during their use, it is advisable to cancel combined oral contraceptives and treat arterial hypertension. The use of combined oral contraceptives can be continued if normal blood pressure values are achieved with the help of antihypertensive therapy.

Effects on the menstrual cycle:

When using combined oral contraceptives, irregular (acyclic) bleeding (“smearing” spotting or “breakthrough” bleeding) may occur, especially during the first months of use. Therefore, any irregular bleeding should only be evaluated after an adjustment period of approximately 3 cycles.

If irregular bleeding recurs or develops after previous regular cycles, a thorough examination should be performed to rule out malignancies or pregnancy.

Some women may not develop “withdrawal” bleeding during the pill break. If the use of combined oral contraceptives was carried out in accordance with the instructions, then pregnancy is unlikely. However, if the use of combined oral contraceptives was carried out irregularly before, or if there are no consecutive “withdrawal” bleeding, then pregnancy should be excluded before continuing to take the drug.

Impact on laboratory test scores:

The use of oral combined contraceptives may affect the results of certain laboratory tests, including biochemical analysis of blood (liver, thyroid, kidney and adrenal function, plasma transport protein concentrations (such as SHBG), carbohydrate metabolism, lipid/lipoprotein fractions), as well as coagulation and fibrinolysis indicators. However, changes in these indicators remain within normal values.

Influence on the ability to drive vehicles and mechanisms:

There are no data on the negative effect of the drug Diecyclen on the ability to drive vehicles and engage in potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Pills.

Active ingredient

Ethinyl Estradiol, Dienogest

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For women of childbearing age, For adults as prescribed by a doctor

Indications

Acne, Contraception, Seborrhea